5-amino-1-β-D-ribofuranosylimidazole-4-carbonitrile | 23192-64-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 咪唑核糖核苷和核糖核苷酸
• 英文名称: 5-amino-1-β-D-ribofuranosylimidazole-4-carbonitrile
• 英文别名: 5-amino-4-cyano-1-(β-D-ribofuranosyl)imidazole；5-amino-1-beta-D-ribofuranosyl-4-cyanoimidazole；5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]imidazole-4-carbonitrile
• CAS: 23192-64-5
• 化学式: C₉H₁₂N₄O₄
• 分子量: 240.219
• InChiKey: HQUFDEULYSDZNH-JXOAFFINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  138
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-amino-1-β-D-ribofuranosylimidazole-4-carbonitrile 在 sodium hydroxide 作用下， 反应 2.5h， 以72%的产率得到阿卡地新
  参考文献：
  名称：

  Nucleosides from carbohydrate adducts of diaminomaleonitrile. A novel synthesis of 5-amino-1-(.beta.-D-ribofuranosyl)imidazole-4-carboxamide and 5-amino-1-(.beta.-D-ribopyranosyl)imidazole-4-carboxamide

  摘要：

  DOI：

  10.1021/jo00206a004
• 作为产物：
  描述：

  阿卡地新 在 4-二甲氨基吡啶 、 sodium methylate 、 三乙胺 、 三氯氧磷 作用下， 生成 5-amino-1-β-D-ribofuranosylimidazole-4-carbonitrile
  参考文献：
  名称：

  Murakami, Teiichi; Otsuka, Masami; Kobayashi, Susumu, Heterocycles, 1981, vol. 16, # 8, p. 1315 - 1319

  摘要：

  DOI：

文献信息

• Synthesis and coronary vasodilating activity of 2-substituted adenosines.
  作者：RYUJI MARUMOTO、YOSHIO YOSHIOKA、OSAMU MIYASHITA、SHUNSUKE SHIMA、KINICHI IMAI、KATSUYOSHI KAWAZOE、MIKIO HONJO

  DOI：10.1248/cpb.23.759

  日期：——

  A large scale preparation of 2-haloadenosines (1) was attained by acetylation of 2-haloinosines (3), followed by chlorination and amination. 2-Alkoxyadenosines (5) were prepared in fairly good yields by protection of both 2'- and 3'-hydroxyl groups of 2-chloroadenosine (1a) or 2-chloroinosine (3a), followed by substitution of the chlorine atom with alkoxy group. In the reaction of 1a with sodium alkoxide, there were obtained some oligomers of 5, of which the structures were elucidated. The reaction of 5-amino-4-cyano-1-β-D-ribofuranosylimidazole with carbon disulfide afforded 2, 6-di-mercapto-9-β-D-ribofuranosylpurine (15), which was converted to 2-mercaptoadenosine (14e) and its S-substituted derivatives. 2-Phenylaminoadenosine (29e) was prepared with comparative ease via 2-phenylamino-2', 3', 5'-tri-O-acetylinosine (32), the synthesis of which was effected by acetylation of 2-phenylaminoinosine (30) with acetylchloride in acetic acid. Many 2-substituted adenosines including O-substituted 2-hydroxyadenosines, S-substituted 2-mercaptoadenosines, N2-substituted 2-aminoadenosines, 2-alkyl- and -aryl-adenosines were prepared, among which several compounds were found to have a remarkable coronary vasodilating potency. Compound (29e) showed not only a strong potency, but also a longer duration of the effect than that of 1a. The structure-coronary vasodilating activity relationship was also discussed.

  通过乙酰化2-卤代次黄嘌呤核苷(3)继以氯化和胺化,制得了2-卤代腺嘌呤核苷(1)的大量样品。通过保护2-氯腺嘌呤核苷(la)或2-氯代次黄嘌呤核苷(3a)的2'-和3'-羟基,然后用烷氧基团取代氯原子,制得了收率相当不错的2-烷氧基腺嘌呤核苷(5)。la与烷醇钠反应,得到5的一些寡聚体,其结构已得到阐明。5-氨基-4-氰基-1-β-D-呋喃核糖基咪唑与二硫化碳反应,生成2,6-二巯基-9-β-D-呋喃核糖基嘌呤(15),可转化为2-巯基腺嘌呤核苷(14e)及其S-取代衍生物。2-苯胺基腺嘌呤核苷(29e)通过2-苯胺基-2',3',5'-三-O-乙酰次黄嘌呤核苷(32)比较容易地制得,而32是通过2-苯胺基次黄嘌呤核苷(30)在乙酸中与乙酰氯反应进行乙酰化来合成的。制备了许多2-取代腺嘌呤核苷,包括O-取代2-羟基腺嘌呤核苷、S-取代2-巯基腺嘌呤核苷、N2-取代2-氨基腺嘌呤核苷、2-烷基和芳基腺嘌呤核苷,其中发现几种化合物具有显著的冠状血管舒张活性。化合物(29e)不仅显示了强大的活性,而且其效果的持续时间比la更长。还讨论了结构-冠状血管舒张活性关系。
• Novel adenosine derivatives and pharmaceutical composition containing
  申请人：Nippon Zoki Pharmaceutical Co., Ltd.

  公开号：US04843066A1

  公开（公告）日：1989-06-27

  Novel adenosine compounds of the formula (I): ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 are hydrogen or a lower alkyl group; X is hydrogen, a lower alkyl group, an amino group or halogen; and Y is hydrogen or a lower alkyl group, exhibit utility as antihypertensive agents.

  新型腺苷化合物的化学式（I）：##STR1## 其中 R.sub.1、R.sub.2 和 R.sub.3 为氢或较低的烷基基团；X 为氢、较低的烷基基团、氨基或卤素；Y 为氢或较低的烷基基团，作为降压药物具有实用性。
• Purines. LXIV. Syntheses of 9-Methyl-2-azaadenine 1-Oxide, Its O-Methyl Derivative, and 1-Substituted 5-Azidoimidazole-4-carboxamides.
  作者：Tohru SAITO、Yayoi ASAHI、Satoshi NAKAJIMA、Tozo FUJII

  DOI：10.1248/cpb.42.2263

  日期：——

  Diazotization of 5-amino-N'-methoxy-1-methylimidazole-4-carboxamidine (4a) with NaNO2 in 1N aqueous HCl was found to give the 1-methoxy-2-azaadenine derivative 8a·HI, which produced 5-azido-1-methylimidazole-4-carbonitrile (5a) on treatment with aqueous Na2CO3. The ribosyl analogue 5b, obtained from the riboside 4b by similar diazotization, was utilized for the synthesis of 5-azido-1-β-D-ribofuranosylimidazole-4-carboxamide (9b), a novel AICA riboside analogue. On heating in HCONMe2 at 70°C for 10min, 8a·HI yielded the 1-N-oxide 7a. Several reactions to transform the functional groups in 5a were also investigated.

  5-氨基-N'-甲氧基-1-甲基咪唑啉-4-甲脒（4a）在1N水合HCl中用NaNO2进行重氮化反应，得到1-甲氧基-2-氮杂腺嘌呤衍生物8a·HI，该物质在处理后与水合Na2CO3反应生成5-叠氮-1-甲基咪唑啉-4-氰化物（5a）。通过类似的重氮化反应从核苷4b得到的核糖类似物5b，被用于合成5-叠氮-1-β-D-呋喃核糖基咪唑啉-4-羧酰胺（9b），这是一种新颖的AICA核苷类似物。在HCONMe2中加热至70°C并保持10分钟，8a·HI生成1-N-氧化物7a。还研究了几种转化5a中功能团的反应。
• Synthesis of 2-phenylaminoadenosine from imidazole nucleosides.
  作者：KIYOSHI OMURA、RYUJI MARUMOTO、YOSHIYASU FURUKAWA

  DOI：10.1248/cpb.29.1870

  日期：——

  Three methods for the synthesis of 2-phenylaminoadenosine (1, CV-1808), a potent coronary vasodilator with prolonged action, were exploited. 1) The reaction of 5-amino-4-cyano-1-(β-D-ribofuranosyl) imidazole (7) with phenyl isothiocyanate gave 7-imino-5-phenylamino-3-(β-D-ribofuranosyl) imidazo [4, 5-d] [1, 3]-thiazine (11), which, on alkaline treatment, rearranged to 6-mercapto-2-phenylamino-9-(β-D-ribofuranosyl) purine (12). On methylation, 12 gave the 6-methylmercapto derivative (14), which was converted to 1 by treatment with ammonia. 2) 5-Amino-4-cyano-1-(β-D-ribofuranosyl) imidazole (7) reacted with phenyl cyanamide in methanolic ammonia, giving 1 and 2-aminoadenosine as a by-product. 3) Ethyl 5-amino-1-(β-D-ribofuranosyl)-4-carboximidate (21b) was directly obtained by treatment of 5-amino-1-(2, 3, 5-tri-O-propionyl-β-D-ribofuranosyl) imidazole-4-carboxamide (4) with Meerwein's reagent followed by deacylation, and this was led to 1 by the reaction with phenyl cyanamide.

  开发了三种合成2-苯胺腺苷（1，CV-1808）的方法，这是一种具有持久作用的强效冠状动脉扩张剂。1）5-氨基-4-氰基-1-（β-D-呋喃核糖基）咪唑（7）与苯基异硫氰酸酯反应，生成7-亚氨基-5-苯胺基-3-（β-D-呋喃核糖基）咪唑并[4,5-d][1,3]噻嗪（11），后者经碱性处理后重排为6-巯基-2-苯胺基-9-（β-D-呋喃核糖基）嘌呤（12）。甲基化后，12生成6-甲硫基衍生物（14），通过氨处理转化为1。2）5-氨基-4-氰基-1-（β-D-呋喃核糖基）咪唑（7）在甲醇氨中与苯基氰胺反应，生成1和2-氨基腺苷作为副产品。3）通过5-氨基-1-（2,3,5-三-O-丙酰基-β-D-呋喃核糖基）咪唑-4-羧酰胺（4）与Meerwein试剂处理后去酰化，直接得到乙基5-氨基-1-（β-D-呋喃核糖基）-4-羧基咪唑盐（21b），然后通过与苯基氰胺反应生成1。
• Synthesis of 2-substituted adenine-arabinosides and related compounds from 5-amino-4-cyano-1-(.BETA.-d-ribofuranosyl)imidazole.
  作者：Yoshiko SATO、Tokumi MARUYAMA、Mikio HONJO

  DOI：10.1248/cpb.37.1604

  日期：——

  Triflation of the N5-benzylidene-3', 5'-O-silyl protected 5-amino-4-cyano-1-(β-D-ribofuranosyl)imidazole (AICN-riboside) (IIb), followed by nucleophilic displacement with OAc- and N3-provided the corresponding 2'(S)-substituted derivatives (VIIa, VIIb). Deprotection of the silyl and benzylidene groups of VIIa, followed by hydrolysis of the acetyl group gave AICN-arabinoside (IXc). Reaction of IXc with alkyl, aryl and aralkyl nitriles afforded the corresponding 2-substituted adenine-arabinosides (XIa-e). The 2'-azido (Xa) and 2'-amino (Xb) analogs of XIa were similarly prepared.

  N5-苄亚基-3', 5'-O-硅保护5-氨基-4-氰基-1-(β-D-核糖基)咪唑（AICN-核苷）（IIb）的三氟化反应，随后与OAc和N3进行亲核取代，得到相应的2'(S)-取代衍生物（VIIa，VIIb）。去保护VIIa中的硅基和苄亚基，随后水解乙酰基，得到AICN-阿拉伯糖苷（IXc）。IXc与烷基、芳基和芳烷基氰化物反应，得到相应的2-取代腺苷-阿拉伯糖苷（XIa-e）。XIa的2'-叠氮（Xa）和2'-氨基（Xb）类似物也以类似方式制备。